The Impact of Prescription Opioid Use on Pregnancy Outcomes

处方阿片类药物的使用对妊娠结局的影响

• 批准号: 9470113
• 负责人: Brian Thomas Bateman
• 金额: $ 57.01万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-15 至 2021-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9470113
• 关键词: Abruptio Placentae; Affect; Biological; Calibration; Clinical; Clinical Data; Clinical Management; Conflict (Psychology); Congenital Abnormality; Congenital clubfoot; Counseling; Data; Dose; Epidemiologic Methods; Epidemiology; Etiology; Exposure to; Fetal Growth Retardation; First Pregnancy Trimester; Gastroschisis; General Population; Goals; Heart Abnormalities; High Prevalence; Holoprosencephaly; Hydrocephalus; Infant; Insurance; Literature; Measures; Medicaid; Medical; Methods; Microcephaly; Morphine; Mothers; Neonatal Abstinence Syndrome; Neural Tube Defects; Neuraxis; Observational Study; Opioid; Outcome; Pain management; Pharmaceutical Preparations; Physiological; Placenta; Pre-Eclampsia; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Pregnant Women; Premature Birth; Relative Risks; Residual state; Risk; Risk Estimate; Safety; Sample Size; Siblings; Small for Gestational Age Infant; Stratification; Teratogens; United States; Woman; adverse outcome; adverse pregnancy outcome; beneficiary; brain malformation; cohort; high dimensionality; high risk; in utero; infant outcome; innovation; malformation; neonatal outcome; offspring; opioid misuse; opioid use; opioid use in pregnancy; pre-clinical; prescription opioid; prescription opioid misuse

ABSTRACT The rapid rise in the use and misuse of prescription opioids in the United States extends to pregnant women. Recent data from our group suggests that 22% of Medicaid beneficiaries and 14% of commercial insurance beneficiaries are exposed to opioids during pregnancy, including up to 10% during the first trimester. Despite the high prevalence of exposure to prescription opioids, little is known about the impact on adverse pregnancy outcomes. Epidemiological and pre-clinical data suggests that such exposure may be associated with higher risk of certain congenital malformations, preterm delivery, small for gestational age, and ischemic placental complications. But data are few and conflicting, and the available literature is limited by concerns related to recall bias, residual confounding bias, and small sample size. Evaluating the impact of prescription opioids using observational data is challenging due to concerns related to potential exposure misclassification due to illicit use and diversion, confounding by indication, and missing information on other relevant confounders. In this study we will utilize innovative, state of the art epidemiological methods to overcome these challenges, generating unbiased or minimally biased estimates of the risk to pregnancy outcomes of exposure to commonly used prescription opioids during etiologically relevant periods of gestation. Specific methods that we intend to employ include high-dimensional propensity score adjustment, propensity score calibration, alternative referents (including sibling and discontinuer comparisons), livebirths sensitivity analyses, propensity score fine stratification, and bias analyses to account for potential misclassification of exposure and outcome. The primary goal of the study is to define the biological effects associated with prescription opioid exposure, independent of confounding factors, which will therefore be relevant to both medical and non- medical use of prescription opioids during pregnancy. To accomplish this, we will use a cohort of 1.8 million pregnancies of Medicaid beneficiaries and a cohort of 1.7 million pregnancies of commercial insurance beneficiaries. We will evaluate the association between prescription opioid exposure during the etiologically relevant window and a variety of important adverse pregnancy outcomes previously hypothesized to be associated with such exposure. We will also assess for the outcomes in relation to specific opioids and will assess the impact of duration of exposure and dose. The results of the studies will have an important and direct clinical impact. Understanding the safety of prescription opioid exposure during pregnancy will guide clinicians' approach to the treatment of pain in pregnancy, will inform the counseling of women who misuse prescription opioids during pregnancy, and will guide the clinical management of opioid exposed women and their offspring.

抽象的 在美国，处方阿片类药物的使用和滥用迅速增加，并延伸至孕妇 女性。我们小组的最新数据表明，22% 的医疗补助受益人和 14% 的商业受益人 保险受益人在怀孕期间会接触阿片类药物，其中在妊娠前三个月接触阿片类药物的比例高达 10%。 尽管接触处方阿片类药物的比例很高，但人们对其不良影响的影响知之甚少。 妊娠结果。流行病学和临床前数据表明，这种暴露可能与 某些先天畸形、早产、小于胎龄和缺血性的风险较高 胎盘并发症。但数据很少且相互矛盾，可用文献也因担忧而受到限制 与回忆偏差、残留混杂偏差和小样本量有关。 由于担忧，使用观察数据评估处方阿片类药物的影响具有挑战性 与由于非法使用和转移而导致的潜在暴露错误分类、指示混淆以及 缺少其他相关混杂因素的信息。在这项研究中，我们将利用创新的、最先进的技术 克服这些挑战的流行病学方法，产生无偏或最小偏倚的估计 在病因相关期间接触常用处方阿片类药物对妊娠结局的风险 妊娠期。我们打算采用的具体方法包括高维倾向评分 调整、倾向评分校准、替代参考对象（包括兄弟姐妹和中止者比较）、 活产敏感性分析、倾向评分精细分层和偏差分析以考虑潜在的可能性 暴露和结果的错误分类。 该研究的主要目标是确定与处方阿片类药物相关的生物效应 暴露，独立于混杂因素，因此与医疗和非相关 怀孕期间处方阿片类药物的医疗用途。为了实现这一目标，我们将使用 180 万的队列 医疗补助受益人的怀孕情况以及商业保险受益人的 170 万怀孕情况 受益人。我们将评估病因学期间处方阿片类药物暴露之间的关联 相关窗口和先前假设的各种重要的不良妊娠结局 与此类暴露相关。我们还将评估与特定阿片类药物相关的结果，并将 评估暴露时间和剂量的影响。 研究结果将产生重要而直接的临床影响。了解安全性 怀孕期间处方阿片类药物暴露将指导临床医生治疗疼痛的方法 怀孕期间，将为在怀孕期间滥用处方阿片类药物的妇女提供咨询，并将 指导阿片类药物暴露妇女及其后代的临床管理。